Adjuvant Therapy of Uveal Melanoma: Current Status.
Ontology highlight
ABSTRACT:
SUBMITTER: Triozzi PL
PROVIDER: S-EPMC4864524 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Publications
Adjuvant Therapy of Uveal Melanoma: Current Status.
Triozzi Pierre L PL Singh Arun D AD
Ocular oncology and pathology 20140910 1
The survival of patients with uveal melanoma remains poor because of the development of metastatic disease. Adjuvant therapy after treatment of the primary tumor has been tested but has not been shown to prevent the development of metastasis. Several new approaches are being developed. Cytotoxic and immunotherapeutic regimens are being more rationally applied using tumor genetic criteria to better identify patients at risk. Trials in the adjuvant setting of novel immunotherapeutic and targeted a ...[more]
Similar Datasets
Project description:BackgroundUveal melanoma is a rare subtype of melanoma. Prognosis and survival rates for patients with metastatic uveal melanoma remain poor. No current FDA-approved standard of care therapy is available for patients with metastatic uveal melanoma. Thus, clinical trials are essential for the development of new therapies and to provide patients hope for improved survival and outcomes.SummaryIn this article, we review clinical trials identified on the database https://clinicaltrials.gov that are open and enrolling patients with metastatic uveal melanoma as of November 26, 2019. This search produced 17 active trials involving liver-directed therapy, CNS-directed therapy, and systemic therapy with immunotherapy, targeted therapy, or oncolytic virus therapy. Here, we discuss liver and CNS-directed therapy as well as systemic targeted therapy and oncolytic virus therapy. Immunotherapy clinical trials are discussed in a companion review article by Dr. Marlana Orloff.Key messagesVarious novel therapeutic targets and immunomodulatory approaches are on the horizon for patients with metastatic uveal melanoma and may yield incremental therapeutic benefit. Selecting a clinical trial must be individualized and made jointly with the patient and his/her oncologist.
| S-EPMC7772871 | biostudies-literature
Project description:IntroductionApproximately 40% of patients with uveal melanoma (UM) will develop metastatic disease. Tumors measuring at least 12mm in basal diameter with a class 2 signature, as defined by a widely used gene expression-profiling test, are associated with significantly higher risk of metastasis, with a median time to recurrence of 32 months. No therapy has been shown to reduce this risk.Materials and methodsThis was a single-arm, multicenter study in patients with high-risk UM who received definitive treatment of primary disease and had no evidence of metastasis. Patients were consecutively enrolled to receive 12 four-week cycles of adjuvant crizotinib at a starting dose of 250mg twice daily and were subsequently monitored for 36 months. The primary outcome of this study was to assess recurrence-free survival (RFS) of patients with high-risk UM who received adjuvant crizotinib.Results34 patients enrolled and received at least one dose of crizotinib. Two patients were unevaluable due to early withdrawal and loss to follow-up, leaving 32 patients evaluable for efficacy. Eight patients (25%) did not complete the planned 48-week course of treatment due to disease recurrence (n=5) or toxicity (n=3). All patients experienced at least one adverse event (AE), with 11/34 (32%) experiencing a Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 AE. After a median duration of follow up of 47.1 months, 21 patients developed distant recurrent disease. The median RFS was 34.9 months (95% CI (Confidence Interval), 23-55 months), with a 32-month recurrence rate of 50% (95% CI, 33-67%). Analysis of protein contents from peripheral blood extracellular vesicles in a subset of patient samples from baseline, on-treatment, and off-treatment, revealed a change in protein content associated with crizotinib exposure, however without a clear association with disease outcome.ConclusionsThe use of adjuvant crizotinib in patients with high-risk UM did not result in improved RFS when compared to historical controls. Analysis of blood extracellular vesicles revealed changes in protein content associated with treatment, raising the possibility of future use as a biomarker. Further investigation of adjuvant treatment options are necessary for this challenging disease.
| S-EPMC9465386 | biostudies-literature
Project description:Uveal melanoma is a common intraocular malignant tumor that is uniformly fatal once metastatic. No effective adjuvant therapy currently exists to reduce the risk of distant metastasis after definitive treatment of the primary lesion. Immunotherapy has been used effectively in the adjuvant setting in locally advanced cutaneous melanoma. We performed a Phase I/II clinical trial of adjuvant ipilimumab in high-risk primary uveal melanoma with distant metastasis-free survival (DMFS) as the primary objective. A total of 10 patients with genomically high-risk disease were treated: three at a dose of 3 mg/kg and seven at 10 mg/kg. Two of the seven patients at the higher dose had to discontinue therapy secondary to grade 3 toxicity. At 36 months follow-up, 80% of patients had no evidence of distant disease (95% CI, 58.7?100). With recent advancements in CTLA-4 inhibition, PD-1 inhibition, and combined checkpoint blockade, immunotherapy is a promising avenue of treatment in uveal melanoma. Further clinical trials are needed to elucidate the role of immunotherapy in the adjuvant setting.
| S-EPMC6406862 | biostudies-literature
Project description:This review describes the progress that the concept of adjuvant therapies has undergone in the last 50 years and focuses on the most recent development where an adjuvant approach has been scientifically evaluated in melanoma clinical trials. Over the past decade the development of immunotherapies and targeted therapies has drastically changed the treatment of stage IV melanoma patients. These successes led to trials studying the same therapies in the adjuvant setting, in high risk resected stage III and IV melanoma patients. Adjuvant immune checkpoint blockade with anti-CTLA-4 antibody ipilimumab was the first drug to show an improvement in recurrence-free and overall survival but this was accompanied by high severe toxicity rates. Therefore, these results were bypassed by adjuvant treatment with anti-PD-1 agents nivolumab and pembrolizumab and BRAF-directed target therapy, which showed even better recurrence-free survival rates with more favorable toxicity rates. The whole concept of adjuvant therapy may be integrated with the new neoadjuvant approaches that are under investigation through several clinical trials. However, there is still no data available on whether the effective adjuvant therapy that patients finally have at their disposal could be offered to them while waiting for recurrence, sparing at least 50% of them a potentially long-term toxic side effect but with the same rate of overall survival (OS). Adjuvant therapy for melanoma has radically changed over the past few years-anti-PD-1 or BRAF-directed therapy is the new standard of care.
| S-EPMC7409361 | biostudies-literature
Project description:Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, with a 10-year cumulative metastatic rate of 34%. The most common site of metastasis is the liver (95%). Unfortunately, the current treatment of metastatic UM is limited by the lack of effective systemic therapy. Options for the management of the primary intraocular tumor include radical surgery as well as conservative treatments in order to preserve visual acuity. For metastatic disease, several approaches have been described with no standard method. Nevertheless, median survival after liver metastasis is poor, being around 4-6 months, with a 1-year survival of 10%-15%. In this review, the authors summarize current and promising new treatments for UM.
| S-EPMC3755706 | biostudies-literature
Project description:Uveal melanoma, which is the most common primary intraocular malignancy in adults, arises from melanocytes within the iris, ciliary body and choroid. The diagnosis is based principally on clinical examination of the tumor with biomicroscopy and indirect ophthalmoscopy and confirmed by diagnostic techniques such as ultrasonography, fundus fluorescein angiography and optical coherence tomography. The clinical diagnosis of posterior uveal melanomas can be made when the classical appearance of a pigmented dome-shaped mass is detected on dilated fundus exam. Uveal melanomas classically show low to medium reflectivity on A-scan ultrasonography and on B-scan ultrasonography the tumor appears as a hyperechoic, acoustically hollow intraocular mass. Management of a suspicious pigmented lesion is determined by its risk factors of transforming into a choroidal melanoma, such as documentation of growth, thickness greater than 2 mm, presence of subretinal fluid, symptoms and orange pigment, margin within 3 mm of the optic disc, and absence of halo and drusen. Advances in the diagnosis and local and systemic treatment of uveal melanoma have caused a shift from enucleation to eye-conserving treatment modalities including transpupillary thermotherapy and radiotherapy over the past few decades. Prognosis can be most accurately predicted by genetic profiling of fine needle aspiration biopsy of the tumor before the treatment, and high-risk patients can now be identified for clinical trials that may lead to target-based therapies for metastatic disease and adjuvant therapy which aims to prevent metastatic disease.
| S-EPMC5076295 | biostudies-other
Project description:Opinion statementIn the past decade, several endocrine treatment regimens have been developed for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, including tamoxifen, aromatase inhibitors (AI), or a combination of these. The standard duration of adjuvant endocrine treatment has been 5 years for a long time. Nevertheless, the high number of recurrences occurring after 5 years suggested that extended endocrine therapy could further improve outcome, which led to the start of several randomized clinical trials investigating the effects of extended use of endocrine therapy. The extended duration of tamoxifen has been shown to improve disease-free survival and overall survival in the ATLAS and aTTom trials. However, in postmenopausal women, AIs have been shown to be more effective when compared with tamoxifen. Based hereon, it is recommended that adjuvant endocrine therapy in postmenopausal women with early breast cancer should include an AI. Recently, the DATA, IDEAL, and NSABP B42 trials showed that extended adjuvant endocrine therapy with AIs beyond 5 years in postmenopausal women with early breast cancer did reduce the occurrence of secondary breast tumors, but had no or only a small impact on distant metastasis free survival. Furthermore, toxicity of adjuvant AIs led to gradually decreasing compliance rates and long-term toxicities to non-breast cancer-related deaths. Therefore, we suggest considering extended adjuvant treatment only in women with high-risk early breast cancer who tolerate treatment well.
| S-EPMC5937869 | biostudies-literature
Project description:The incidence of melanoma is rapidly increasing, especially in younger female and older male patients. Recent fundamental advances in our knowledge of melanoma tumorigenesis have established roles for inhibitors of the MAPK pathway and regulatory immune checkpoints CTLA-4 and PD-1/PD-L1. However, the majority of patients continue to present with non-metastatic disease-typically managed with surgical resection and adjuvant therapy. High-dose IFN-α2b (HDI) is the main adjuvant therapeutic mainstay in high-risk disease following definitive resection. In this chapter, we review the evidence supporting the use of adjuvant HDI in high-risk melanoma. We also discuss some of the other treatment modalities that have been evaluated including vaccines, chemotherapy, and radiotherapy.
| S-EPMC8603200 | biostudies-literature
Project description:Estimates from the U.S. Surveillance, Epidemiology, and End Results registry suggest that melanoma incidence will reach 70,230 cases in 2011, of whom 8790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society.High-dose interferon-α-2b is the only agent approved for adjuvant therapy for melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However, toxicity affects compliance, and current research is focusing on biomarkers that may allow selection of patients with greater likelihood of response and exploring new agents either singly or in combination that may improve on the benefit of interferon.In this article, we review the data for the adjuvant therapy for malignant melanoma--focusing on the results obtained with various regimens testing the several formulations of interferon-α2 and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway.
| S-EPMC3478763 | biostudies-literature
Project description:The global incidence of malignant melanoma, the leading cause of skin cancer death, has steadily increased in recent years. Surgical excision is the treatment of choice for early-stage melanoma. However, 40-60% of patients with high-risk melanoma or with nodal involvement eventually experience loco-regional relapse or tumor progression. Adjuvant therapy aims to reduce the rate of recurrence in radically operated high-risk patients with melanoma and thus improves survival. Interferon-α has long been the only approved drug for adjuvant melanoma therapy, despite an unclear survival benefit. The landmark success of immune-checkpoint inhibitors and BRAF/MEK-directed targeted therapies in the treatment of patients with stage IV melanoma led to the initiation of clinical trials in the adjuvant setting. These trials demonstrated the efficacy of immune-checkpoint inhibitors and targeted therapies for the adjuvant treatment of high-risk patients with melanoma, as shown both by an increase in recurrence-free survival and the emergence of long-term survivors, finally resulting in the approval of the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab, PD1 inhibitors (nivolumab, pembrolizumab), and BRAF/MEK inhibitors for adjuvant melanoma therapy. This review aims to delineate the advances in adjuvant melanoma therapy, issuing particularly recent results from clinical trials. Moreover, we also discuss pending issues and future challenges, which comprise the adequate selection of adjuvant regimens for patient subgroups and the identification of markers likely to predict the individual response to adjuvant treatments. Last, we outline the role of emerging neoadjuvant approaches, which may complement adjuvant strategies and are currently investigated in clinical trials.
| S-EPMC8484171 | biostudies-literature